The potential of ionizing radiation as a carcinogen is well established. However, to date, there is no real understanding of the underlying molecular basis of this process. The goal of this project is to identify oncogenes isolated from transformed cell lines induced by ionizing radiation and to characterize the molecular changes in these genes. One goal is to establish whether radiation leaves a "molecular signature" on the DNA of transformed cells, by inducing either a unique oncogene(s) or alters a known oncogene(s) in a unique way. The strategy proposed in this application for oncogene isolation has been used successfully by this laboratory to isolate a sequence containing an oncogene, from a gamma-ray transformed C3H 10T1/2 cell line. In addition to continuing the characterization of this gene several parallel studies will be carried out. First, other gamma-ray transformed cell lines will be screened to determine if the same alteration has occurred or whether a different mechanism was involved in their transformation. Second, the results found with gamma-ray transformants will be used to screen high LET radiation transformed cell lines. Third, activated oncogenes in alpha-particle and other gamma-ray transformed cell lines will be characterized. Fourth, the molecular basis of transformation in human cells will be examined.